Intra-Articular Blockade of P2X7 Receptor Reduces the Articular Hyperalgesia and Inflammation in the Knee Joint Synovitis Especially in Female Rats

Autor(es)

Teixeira, Juliana Maia ; Dias, Elayne Vieira ; Parada, Carlos Amilcar ; Tambeli, Claudia Herrera

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PAIN; v. 18, n. 2, p. 132-143, FEB 2017.
• Citações Web of Science: 9

Resumo

Synovitis is a key factor in joint disease pathophysiology, which affects a greater proportion of women than men. P2X7 receptor activation contributes to arthritis, but whether it plays a role in articular inflammatory pain in a sex-dependent manner is unknown. We investigated whether the P2X7 receptor blockade in the knee joint of male and female rats reduces the articular hyperalgesia and inflammation induced by a carrageenan knee joint synovitis model. Articular hyperalgesia was quantified using the rat knee joint incapacitation test and the knee joint inflammation, characterized by the concentration of cytokines tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and cytokine-induced neutrophil chemoattractant-1, and by neutrophil migration, was quantified using enzyme linked immunosorbent assay and by myeloperoxidase enzyme activity measurement, respectively. P2X7 receptor blockade by the articular coadministration of selective P2X7 receptor antagonist A740003 with carrageenan significantly reduced articular hyperalgesia, pro-inflammatory cytokine concentrations, and myeloperoxidase activity induced by carrageenan injection into the knee joint of male and estrus female rats. However, a lower dose of P2X7 receptor antagonist was sufficient to significantly induce the antihyperalgesic and anti-inflammatory effects in estrus female but not in male rats. These results suggest that P2X7 receptor activation by endogenous adenosine 5'-triphos-phate is essential to articular hyperalgesia and inflammation development in the knee joint of male and female rats. However, female rats are more responsive than male rats to the antihyperalgesic and anti-inflammatory effects induced by P2X7 receptor blockade. Perspective: P2X7 receptors could be promising therapeutic targets in the treatment of knee joint disease symptoms, especially in women, who are more affected than men by these conditions. (C) 2016 by the American Pain Society (AU)

• Processo FAPESP: 10/05381-4 - Participação dos receptores purinérgicos P2X3 e P2X7 na artrite induzida por carragenina em joelho de ratos
• Beneficiário: Claudia Herrera Tambeli
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/16854-3 - Participação dos receptores purinérgicos P2X3 e P2X7 na artrite induzida por carragenina em joelho de ratos
• Beneficiário: Juliana Maia Teixeira
• Modalidade de apoio: Bolsas no Brasil - Doutorado